tbuckley/cabot-search huggingface dataset:
Somatostatin Receptor PET/MR Imaging of Inflammation in Patients With Large Vessel Vasculitis and Atherosclerosis
Authors: Andrej Ćorović, Christopher Wall, Meritxell Nus, Deepa Gopalan, Yuan Huang, Maria Imaz, Michal Zulcinski, Marta Peverelli, Anna Uryga, Jordi Lambert, Dario Bressan, Robert T. Maughan, Charis Pericleous, Suraiya Dubash, Natasha Jordan, David R. Jayne, Stephen P. Hoole, Patrick A. Calvert, Andrew F. Dean, Doris Rassl, Tara Barwick, Mark Iles, Mattia Frontini, Greg Hannon, Roido Manavaki, Tim D. Fryer, Luigi Aloj, Martin J. Graves, Fiona J. Gilbert, Marc R. Dweck, David E. Newby, Zahi A. Fayad, Gary Reynolds, Ann W. Morgan, Eric O. Aboagye, Anthony P. Davenport, Helle F. Jørgensen, Ziad Mallat, Martin R. Bennett, James E. Peters, James H.F. Rudd, Justin C. Mason, Jason M. Tarkin
Journal: Journal of the American College of Cardiology (2023)

Assessing inflammatory disease activity in large vessel vasculitis (LVV) can be challenging by conventional measures. We aimed to investigate somatostatin receptor 2 (SST2) as a novel inflammation-specific molecular imaging target in LVV. In a prospective, observational cohort study, in vivo arterial SST2 expression was assessed by positron emission tomography/magnetic resonance imaging (PET/MRI) using 68Ga-DOTATATE and 18F-FET-βAG-TOCA. Ex vivo mapping of the imaging target was performed using immunofluorescence microscopy; imaging mass cytometry; and bulk, single-cell, and single-nucleus RNA sequencing. Sixty-one participants (LVV: n = 27; recent atherosclerotic myocardial infarction of ≤2 weeks: n = 25; control subjects with an oncologic indication for imaging: n = 9) were included. Index vessel SST2 maximum tissue-to-blood ratio was 61.8% (P < 0.0001) higher in active/grumbling LVV than inactive LVV and 34.6% (P = 0.0002) higher than myocardial infarction, with good diagnostic accuracy (area under the curve: ≥0.86; P < 0.001 for both). Arterial SST2 signal was not elevated in any of the control subjects. SST2 PET/MRI was generally consistent with 18F-fluorodeoxyglucose PET/computed tomography imaging in LVV patients with contemporaneous clinical scans but with very low background signal in the brain and heart, allowing for unimpeded assessment of nearby coronary, myocardial, and intracranial artery involvement. Clinically effective treatment for LVV was associated with a 0.49 ± 0.24 (standard error of the mean [SEM]) (P = 0.04; 22.3%) reduction in the SST2 maximum tissue-to-blood ratio after 9.3 ± 3.2 months. SST2 expression was localized to macrophages, pericytes, and perivascular adipocytes in vasculitis specimens, with specific receptor binding confirmed by autoradiography. SSTR2-expressing macrophages coexpressed proinflammatory markers. SST2 PET/MRI holds major promise for diagnosis and therapeutic monitoring in LVV. (PET Imaging of Giant Cell and Takayasu Arteritis [PITA], NCT04071691; Residual Inflammation and Plaque Progression Long-Term Evaluation [RIPPLE], NCT04073810)
Worsening Heart Failure: Nomenclature, Epidemiology, and Future Directions
Authors: Stephen J. Greene, Johann Bauersachs, Jasper J. Brugts, Justin A. Ezekowitz, Carolyn S.P. Lam, Lars H. Lund, Piotr Ponikowski, Adriaan A. Voors, Faiez Zannad, Shelley Zieroth, Javed Butler
Journal: Journal of the American College of Cardiology (2023)

Heart failure (HF) is a progressive disease characterized by variable durations of symptomatic stability often punctuated by episodes of worsening despite continued therapy. These periods of clinical worsening are increasingly recognized as a distinct phase in the history of HF, termed worsening HF (WHF). The definition of WHF continues to evolve from a historical focus solely on hospitalization to now include nonhospitalization events (eg, need for intravenous diuretic therapy in the emergency or outpatient setting). Most HF clinical trials to date have had HF hospitalization and death as primary endpoints, and only recently, some studies have included other WHF events regardless of location of care. This article reviews the evolution of the WHF definition, highlights the importance of considering the onset of WHF as an event that marks a new phase of HF, summarizes the latest clinical trials investigating novel therapies, and outlines unmet needs regarding identification and treatment of WHF.
Effect of Mini-Dose Ready-to-Use Liquid Glucagon on Preventing Exercise-Associated Hypoglycemia in Adults With Type 1 Diabetes
Authors: Ronnie Aronson, Michael C. Riddell, Valentina Conoscenti, M. Khaled Junaidi
Journal: Diabetes Care (2023)

OBJECTIVE To determine effect of mini-dose, ready-to-use glucagon on incidence of exercise-associated hypoglycemia (EAH) in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS Individuals initially participated in the in-clinic training phase for which they were randomly assigned to a crossover design: 150 µg glucagon (treatment arm A) or placebo (arm B) subcutaneously, immediately before exercise, plus 50% reduction in continuous subcutaneous insulin infusion (CSII) basal delivery rate. Completers were then rerandomly assigned in the 12-week outpatient investigational phase: arm A, B, or open-label C, 150 µg glucagon alone. Participants were to undertake their usual aerobic exercise at moderate to high intensity for 30 to 75 min in real-world settings. Data were analyzed for incidence of level 1 hypoglycemia based on self-monitoring blood glucose and for various secondary and exploratory end points. RESULTS Of 48 participants who completed the training phase, 45 continued to the outpatient phase. For all exercise sessions in the outpatient phase (n = 795), incidence of level 1 hypoglycemia was lower in both glucagon arms (A, 12% [P &amp;lt; 0.0001]; C, 16% [P = 0.0032]) than in the placebo arm (B, 39%). Times below range, in range, and above range from 0 to 300 min did not significantly differ among treatment arms. Consumed grams of exercise carbohydrates were lower with glucagon use than with placebo use but did not reach statistical significance (P = 0.12). Adverse events were similar among treatment arms. CONCLUSIONS Mini-dose glucagon with or without 50% reduction in CSII basal delivery rate may help to decrease EAH incidence in adults with type 1 diabetes.
Letter by Halushka and Witwer Regarding Article, “Circulating MicroRNA-122-5p Is Associated With a Lack of Improvement in Left Ventricular Function After Transcatheter Aortic Valve Replacement and Regulates Viability of Cardiomyocytes Through Extracellular Vesicles”
Authors: Marc K. Halushka, Kenneth W. Witwer
Journal: Circulation (2023)
Is daytime napping an effective strategy to improve sport-related cognitive and physical performance and reduce fatigue? A systematic review and meta-analysis of randomised controlled trials
Authors: Arthur Eumann Mesas, Sergio Núñez de Arenas-Arroyo, Vicente Martinez-Vizcaino, Miriam Garrido-Miguel, Ruben Fernández-Rodríguez, Bruno Bizzozero-Peroni, Ana I Torres-Costoso
Journal: British Journal of Sports Medicine (2023)

Objective To estimate the association between daytime napping and cognitive and physical sport performance and fatigue after normal sleep and partial sleep deprivation (less sleep duration than necessary). Design Systematic review and meta-analysis. Data sources The PubMed, Scopus, Web of Science, Cochrane Central, SportDiscus and PsycINFO databases. Eligibility criteria for selecting studies Randomised controlled trials on the effect of daytime napping on sport performance and fatigue available from inception to 2 December 2022. Standardised mean differences (SMD) and their 95% compatibility intervals (CI) were estimated with the DerSimonian-Laird method through random effect models. Results In the 22 included trials, 291 male participants (164 trained athletes and 127 physically active adults) aged between 18 and 35 years were studied. When performed after a normal night of sleep, napping from 12:30 hours to 16:50 hours (with 14:00 hours being the most frequent time) improved cognitive (SMD=0.69, 95% CI: 0.37 to 1.00; I 2 =71.5%) and physical performance (SMD=0.99, 95% CI: 0.67 to 1.31; I 2 =89.1%) and reduced the perception of fatigue (SMD=−0.76, 95% CI: −1.24 to –0.28; I 2 =89.5%). The positive effects of napping were also confirmed after partial sleep deprivation. Overall, the benefits were higher with a nap duration between 30 and &lt;60 min and when the time from nap awakening to test was greater than 1 hour. Conclusions After a night of normal sleep or partial sleep deprivation, a daytime nap between 30 and &lt;60 min has a moderate-to-high effect on the improvement of cognitive performance and physical performance and on the reduction of perceived fatigue. PROSPERO registration number CRD42020212272.
Hepatic pIgR-mediated secretion of IgA limits bacterial translocation and prevents ethanol-induced liver disease in mice
Authors: Tim Hendrikx, Sonja Lang, Dragana Rajcic, Yanhan Wang, Sara McArdle, Kenneth Kim, Zbigniew Mikulski, Bernd Schnabl
Journal: Gut (2023)

Objective Alcohol-associated liver disease is accompanied by microbial dysbiosis, increased intestinal permeability and hepatic exposure to translocated microbial products that contribute to disease progression. A key strategy to generate immune protection against invading pathogens is the secretion of IgA in the gut. Intestinal IgA levels depend on the polymeric immunoglobulin receptor (pIgR), which transports IgA across the epithelial barrier into the intestinal lumen and hepatic canaliculi. Here, we aimed to address the function of pIgR during ethanol-induced liver disease. Design pIgR and IgA were assessed in livers from patients with alcohol-associated hepatitis and controls. Wild-type and pIgR -deficient ( pIgR -/- ) littermates were subjected to the chronic-binge (NIAAA model) and Lieber-DeCarli feeding model for 8 weeks. Hepatic pIgR re-expression was established in pIgR -/- mice using adeno-associated virus serotype 8 (AAV8)-mediated pIgR expression in hepatocytes. Results Livers of patients with alcohol-associated hepatitis demonstrated an increased colocalisation of pIgR and IgA within canaliculi and apical poles of hepatocytes. pIgR -deficient mice developed increased liver injury, steatosis and inflammation after ethanol feeding compared with wild-type littermates. Furthermore, mice lacking pIgR demonstrated increased plasma lipopolysaccharide levels and more hepatic bacteria, indicating elevated bacterial translocation. Treatment with non-absorbable antibiotics prevented ethanol-induced liver disease in pIgR -/- mice. Injection of AAV8 expressing pIgR into pIgR -/- mice prior to ethanol feeding increased intestinal IgA levels and ameliorated ethanol-induced steatohepatitis compared with pIgR -/- mice injected with control-AAV8 by reducing bacterial translocation. Conclusion Our results highlight that dysfunctional hepatic pIgR enhances alcohol-associated liver disease due to impaired antimicrobial defence by IgA in the gut.
Empirical polymyxin B therapy in febrile neutropenic patients with hematological diseases: A prospective, multicenter, observational clinical study
Authors: Liya Ma, Jianping Shen, Huifang Jiang, Shenxian Qian, Jin Zhang, Jianping Lan, Hua Zhou, Wei Lang, Chen Mei, Xinping Zhou, Lixia Zhu, Gaixiang Xu, Li Ye, Chao Hu, Yanling Ren, Xiudi Yang, Jie Jin, Xiujin Ye, Hongyan Tong
Journal: Journal of Infection (2023)
Pyramidal cell types drive functionally distinct cortical activity patterns during decision-making
Authors: Simon Musall, Xiaonan R. Sun, Hemanth Mohan, Xu An, Steven Gluf, Shu-Jing Li, Rhonda Drewes, Emma Cravo, Irene Lenzi, Chaoqun Yin, Björn M. Kampa, Anne K. Churchland
Journal: Nature Neuroscience (2023)

Abstract Understanding how cortical circuits generate complex behavior requires investigating the cell types that comprise them. Functional differences across pyramidal neuron (PyN) types have been observed within cortical areas, but it is not known whether these local differences extend throughout the cortex, nor whether additional differences emerge when larger-scale dynamics are considered. We used genetic and retrograde labeling to target pyramidal tract, intratelencephalic and corticostriatal projection neurons and measured their cortex-wide activity. Each PyN type drove unique neural dynamics, both at the local and cortex-wide scales. Cortical activity and optogenetic inactivation during an auditory decision task revealed distinct functional roles. All PyNs in parietal cortex were recruited during perception of the auditory stimulus, but, surprisingly, pyramidal tract neurons had the largest causal role. In frontal cortex, all PyNs were required for accurate choices but showed distinct choice tuning. Our results reveal that rich, cell-type-specific cortical dynamics shape perceptual decisions.
Allogeneic BCMA-targeting CAR T cells in relapsed/refractory multiple myeloma: phase 1 UNIVERSAL trial interim results
Authors: Sham Mailankody, Jeffrey V. Matous, Saurabh Chhabra, Michaela Liedtke, Surbhi Sidana, Olalekan O. Oluwole, Shahbaz Malik, Rajneesh Nath, Faiz Anwer, Jose Carlos Cruz, Myo Htut, Erin E. Karski, Wade Lovelace, Myles Dillon, Eric Butz, Wendy Ying, Arun Balakumaran, Shaji K. Kumar
Journal: Nature Medicine (2023)
Assessment of photopsia (flashing lights)
Authors: Jonathan K Y Ng, Peiting Joanne Xie, Ahmed Saber, James Huxtable
Journal: BMJ (2023)

### What you need to know ### Case 1 A man in his 60s with myopia, who had cataract surgery to his right eye a month earlier, presents with two weeks of intermittent arc-like flashes of light in the right eye. He says the flashes are more prominent in dim conditions. Visual acuity in the right eye is 6/6 unaided. Dilated fundus examination reveals a retinal tear. He is treated with an immediate laser retinopexy to prevent a retinal detachment. ### Case 2 A man in his 60s who smokes daily and has hypertension and diabetes mellitus develops three episodes of visual disturbance over a week. He describes them as sudden light flickering on the right side of both eyes lasting two minutes—with nausea, vertigo, occipital headache, and loss of sensation on his left side. He has been well between episodes and has no deficits on examination. Magnetic resonance imaging of his brain shows no acute infarct, but shows atherosclerotic mid-basilar and left posterior cerebral artery stenosis and multiple chronic infarcts. He is diagnosed with vertebrobasilar insufficiency and given antiplatelet medication, a statin, and guidance on smoking cessation. Photopsia is a common presenting symptom in general practice and emergency departments,1 and can be caused by several ocular and systemic conditions, some of which can be threatening to sight or life (box 1). Research specific to photopsia is limited to case series and expert opinion data. The guidance in this article is based on the available evidence and the authors’ clinical experience. Box 1 ### Sight threatening and life threatening causes of photopsia #### Potentially sight threateningRETURN TO TEXT
Correction:<i>Impact of biological therapy on work outcomes in patients with axial spondyloarthritis: results from the British Society for Rheumatology Biologics Register (BSRBR-AS) and meta-analysis</i>
Journal: Annals of the Rheumatic Diseases (2023)

The correct figure 3 and text:Forest plot comparing changes in WPAI outcomes between patients in the biologic and nonbiologic treatment groups.In contrast, there was no improvement in absenteeism in either treatment group; absolute change in TNFi therapy and non-TNFi therapy groups across studies were -2.2% and -2.5%, respectively, and the pooled change in absenteeism was similar in both groups (MD=-1.59,95% CI -5.97, 2.79) (Amended Figure 3).The corrected values are presented in highlight.
Diabetes insipidus and Guillain-Barré-like syndrome following CAR-T cell therapy: a case report
Authors: Christian Koch, Juliane Fleischer, Todor Popov, Karl Frontzek, Bettina Schreiner, Patrick Roth, Markus G. Manz, Simone Unseld, Antonia M. S. Müller, Norman F. Russkamp
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common adverse event of CD19-directed chimeric antigen receptor (CAR) T cell therapy. Other neurological adverse events, however, have not methodically been described and studied. Furthermore, safety data on CAR-T cell therapy in patients with central nervous system (CNS) lymphoma remain limited. Main body We here report occurrence of a Guillain-Barré-like syndrome (GBS) and central diabetes insipidus (cDI) following tisagenlecleucel therapy for relapsed high-grade lymphoma with CNS involvement. Both complications were refractory to standard treatment of ICANS. Weakness of respiratory muscles required mechanical ventilation and tracheostomy while cDI was treated with desmopressin substitution for several weeks. Muscle-nerve biopsy and nerve conduction studies confirmed an axonal pattern of nerve damage. T cell-rich infiltrates and detection of the CAR transgene in muscle-nerve sections imply a direct or indirect role of CAR-T cell-mediated inflammation. In line with current treatment guidelines for GBS, intravenous immunoglobulin was administered and gradual but incomplete recovery was observed over the course of several months. Conclusions This case report highlights the risk of rare but severe neurological adverse events, such as acute GBS or cDI, in patients treated with CAR-T cells. It further underlines the importance of appropriate patient surveillance and systematic reporting of rare complications to eventually improve treatment.
Author Correction: PHYTOCHROME-INTERACTING FACTORs trigger environmentally responsive chromatin dynamics in plants
Authors: Björn C. Willige, Mark Zander, Chan Yul Yoo, Amy Phan, Renee M. Garza, Shelly A. Wanamaker, Yupeng He, Joseph R. Nery, Huaming Chen, Meng Chen, Joseph R. Ecker, Joanne Chory
Journal: Nature Genetics (2023)
Upper respiratory tract mucosal immunity for SARS-CoV-2 vaccines
Authors: Rupsha Fraser, Aurelio Orta-Resendiz, Alexander Mazein, David H. Dockrell
Journal: Trends in Molecular Medicine (2023)

SARS-CoV-2 vaccination significantly reduces morbidity and mortality, but has less impact on viral transmission rates, thus aiding viral evolution, and the longevity of vaccine-induced immunity rapidly declines. Immune responses in respiratory tract mucosal tissues are crucial for early control of infection, and can generate long-term antigen-specific protection with prompt recall responses. However, currently approved SARS-CoV-2 vaccines are not amenable to adequate respiratory mucosal delivery, particularly in the upper airways, which could account for the high vaccine breakthrough infection rates and limited duration of vaccine-mediated protection. In view of these drawbacks, we outline a strategy that has the potential to enhance both the efficacy and durability of existing SARS-CoV-2 vaccines, by inducing robust memory responses in the upper respiratory tract (URT) mucosa.
An atlas of lamina-associated chromatin across twelve human cell types reveals an intermediate chromatin subtype
Authors: Parisha P. Shah, Kathleen C. Keough, Ketrin Gjoni, Garrett T. Santini, Richard J. Abdill, Nadeera M. Wickramasinghe, Carolyn E. Dundes, Ashley Karnay, Angela Chen, Rachel E. A. Salomon, Patrick J. Walsh, Son C. Nguyen, Sean Whalen, Eric F. Joyce, Kyle M. Loh, Nicole Dubois, Katherine S. Pollard, Rajan Jain
Journal: Genome biology (2023)

Association of chromatin with lamin proteins at the nuclear periphery has emerged as a potential mechanism to coordinate cell type-specific gene expression and maintain cellular identity via gene silencing. Unlike many histone modifications and chromatin-associated proteins, lamina-associated domains (LADs) are mapped genome-wide in relatively few genetically normal human cell types, which limits our understanding of the role peripheral chromatin plays in development and disease.
Making machine learning matter to clinicians: model actionability in medical decision-making
Authors: Daniel E. Ehrmann, Shalmali Joshi, Sebastian D. Goodfellow, Mjaye L. Mazwi, Danny Eytan
Journal: npj Digital Medicine (2023)

Abstract Machine learning (ML) has the potential to transform patient care and outcomes. However, there are important differences between measuring the performance of ML models in silico and usefulness at the point of care. One lens to use to evaluate models during early development is actionability, which is currently undervalued. We propose a metric for actionability intended to be used before the evaluation of calibration and ultimately decision curve analysis and calculation of net benefit. Our metric should be viewed as part of an overarching effort to increase the number of pragmatic tools that identify a model’s possible clinical impacts.
Obituary: Jörg Kleine‐Tebbe
Authors: Stephanie Dramburg, Susanne Lau, Paolo Matricardi, Margitta Worm, Cezmi A. Akdis, Claus Bachert, Bruce Bochner, Stephen Durham, Johannes Ring, Heimo Breiteneder, Rudolf Valenta, Claudia Traidl‐Hoffman
Journal: Allergy (2023)
Protein degradation: expanding the toolbox to restrain cancer drug resistance
Authors: Hui Ming, Bowen Li, Jingwen Jiang, Siyuan Qin, Edouard C. Nice, Weifeng He, Tingyuan Lang, Canhua Huang
Journal: Journal of Hematology & Oncology (2023)

Abstract Despite significant progress in clinical management, drug resistance remains a major obstacle. Recent research based on protein degradation to restrain drug resistance has attracted wide attention, and several therapeutic strategies such as inhibition of proteasome with bortezomib and proteolysis-targeting chimeric have been developed. Compared with intervention at the transcriptional level, targeting the degradation process seems to be a more rapid and direct strategy. Proteasomal proteolysis and lysosomal proteolysis are the most critical quality control systems responsible for the degradation of proteins or organelles. Although proteasomal and lysosomal inhibitors (e.g., bortezomib and chloroquine) have achieved certain improvements in some clinical application scenarios, their routine application in practice is still a long way off, which is due to the lack of precise targeting capabilities and inevitable side effects. In-depth studies on the regulatory mechanism of critical protein degradation regulators, including E3 ubiquitin ligases, deubiquitylating enzymes (DUBs), and chaperones, are expected to provide precise clues for developing targeting strategies and reducing side effects. Here, we discuss the underlying mechanisms of protein degradation in regulating drug efflux, drug metabolism, DNA repair, drug target alteration, downstream bypass signaling, sustaining of stemness, and tumor microenvironment remodeling to delineate the functional roles of protein degradation in drug resistance. We also highlight specific E3 ligases, DUBs, and chaperones, discussing possible strategies modulating protein degradation to target cancer drug resistance. A systematic summary of the molecular basis by which protein degradation regulates tumor drug resistance will help facilitate the development of appropriate clinical strategies.
Hepatitis D virus interferes with hepatitis B virus RNA production via interferon-dependent and -independent mechanisms
Authors: Julie Lucifora, Dulce Alfaiate, Caroline Pons, Maud Michelet, Ricardo Ramirez, Floriane Fusil, Fouzia Amirache, Axel Rossi, Anne-Flore Legrand, Emilie Charles, Serena Vegna, Rayan Farhat, Michel Rivoire, Guillaume Passot, Nicolas Gadot, Barbara Testoni, Charlotte Bach, Thomas F. Baumert, Anastasia Hyrina, Rudolf K. Beran, Fabien Zoulim, Andre Boonstra, Hildegard Büning, Eloi R. Verrier, François-Loïc Cosset, Simon P. Fletcher, Anna Salvetti, David Durantel
Journal: Journal of Hepatology (2023)